Investigation of the complex structure, comparative DNA-binding and DNA cleavage of two water-soluble mono-nuclear lanthanum(III) complexes and cytotoxic activity of chitosan-coated magnetic nanoparticles as drug delivery for the complexes

Spectrochim Acta A Mol Biomol Spectrosc. 2017 May 5:178:125-135. doi: 10.1016/j.saa.2017.01.037. Epub 2017 Jan 21.

Abstract

Two water-soluble mono-nuclear macrocyclic lanthanum(III) complexes of 2,6-diformyl-4-methylphenol with 1,3-diamino-2-propanol (C1) or 1,3-propylenediamine (C2) were synthesized and characterized by UV-Vis, FT-IR, 13C and 1H NMR spectroscopy and elemental analysis. C1 complex was structurally characterized by single-crystal X-ray diffraction, which revealed that the complex was mononuclear and ten-coordinated. The coordination sites around lanthanum(III) were occupied with a five-dentate ligand, two bidentate nitrates, and one water molecule. The interaction of complexes with DNA was studied in buffered aqueous solution at pH7.4. UV-Vis absorption spectroscopy, emission spectroscopy, circular dichroism (CD) and viscometric measurements provided clear evidence of the intercalation mechanism of binding. The obtained intrinsic binding constants (Kb) 9.3×103 and 1.2×103M-1 for C1 and C2, respectively confirmed that C1 is better intercalator than C2. The DNA docking studies suggested that the complexes bind with DNA in a groove binding mode with the binding affinity of C1>C2. Moreover, agarose gel electrophoresis study of the DNA-complex for both compounds revealed that the C1 intercalation cause ethidium bromide replacement in a competitive manner which confirms the suggested mechanism of binding. Finally, the anticancer experiments for the treated cancerous cell lines with both synthesized compounds show that these hydrophilic molecules need a suitable carrier to pass through the hydrophobic nature of cell membrane efficiently.

Keywords: Binding constant; Chitosan; Cytotoxicity; DNA cleavage; Lanthanum(III); Molecular docking.

MeSH terms

  • Cell Death / drug effects
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Chitosan / chemistry*
  • Circular Dichroism
  • Coordination Complexes / chemistry*
  • Coordination Complexes / pharmacology*
  • Crystallography, X-Ray
  • DNA / metabolism*
  • DNA Cleavage*
  • Drug Delivery Systems*
  • Electrons
  • Humans
  • Iodides / chemistry
  • Kinetics
  • Lanthanum / chemistry*
  • Magnetite Nanoparticles / chemistry*
  • Molecular Conformation
  • Molecular Docking Simulation
  • Osmolar Concentration
  • Spectrometry, Fluorescence
  • Viscosity
  • Water / chemistry

Substances

  • Coordination Complexes
  • Iodides
  • Magnetite Nanoparticles
  • Water
  • Lanthanum
  • DNA
  • Chitosan